PMDD turns out to be less about bodily symptoms and more about mood and behavior. Dr. David Rubinow, University of North Carolina at Chapel Hill School of Medicine Psychiatry chair studies how hormone changes -and not their levels- can trigger PMDD symptoms in some women.

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Newswise — A new clinical trial at the University of North Carolina at Chapel Hill using a popular low-dose contraceptive could uncover a more effective treatment for the 5 to 10 percent of women who suffer from premenstrual dysphoric disorder (PMDD).

PMDD is much more severe than premenstrual syndrome, or PMS. The disorder interferes with a woman's ability to function effectively several days out of each month, every month. Physical symptoms include bloating, low energy, heart palpitations and joint or muscle pain. Far more disruptive emotional symptoms include irritability, anxiety, depression, mood swings, difficulty focusing and trouble sleeping. For many women with PMDD, five or more of these symptoms occur the week before menstruation starts and disappear a few days after the period begins.

The National Institute of Mental Health awarded UNC a $3 million grant for a five-year clinical trial using a low-dose contraceptive called YAZ (ethinyl estradiol/drospirenone). The trial is based on previous research by David Rubinow, M.D., the Asad Meymandi Distinguished Professor and chair of psychiatry in the UNC School of Medicine.

Rubinow discovered it is the change in " not the level of " reproductive hormones that triggers depression in women who are susceptible to PMDD. In other words, women with the disorder don't have abnormal levels of reproductive hormones, but are more sensitive to the shifts in them that occur prior to menstruation. That sensitivity triggers mood symptoms.

"This study will potentially demonstrate that it is the regimen of administration of birth control pills rather than their specific formulation that results in successful treatment of PMDD," Rubinow said. His colleague and fellow co-principal investigator of the trial, Susan Girdler, Ph.D., professor of psychiatry, added: "If we can eliminate the hormone cycling, we should eliminate the PMDD symptoms."

There are no other studies of continuous administration of birth control pills, so the ability of the study to identify the role of neurosteroids like allopregnanolone (a metabolite of progesterone) in PMDD is unique.

During the trial, researchers will test three groups of 27 women for a three-month period. One group will take a full 28-day dose of oral contraceptives continuously, while another takes the standard 21-7 regimen each month. A third group will be given a placebo.

After the three months, researchers will measure hormone cycling, as well as metabolites of progesterone, which are involved in activating brain centers. "They're regulators of mood and emotion, so if you can eliminate the metabolites that have been implicated in PMDD you may create a huge benefit for women with PMDD," Girdler said.

"We believe this trial will help us understand the underlying physiology, which will allow for the development of a range of possible new treatments," Rubinow added.

That's good news for women like Jamie Dilweg of Chapel Hill, N.C.

Dilweg has managed the disease for 22 years. "Initially, I focused on physical symptoms," she said. "I'd gain weight. My face would be puffy. I had horrible cramps. And that would get me mentally down. The symptoms changed as I matured and had children. It gradually became more emotional. Now it also affects my mental acuity and I can still get down sometimes."

Dilweg's symptoms are fairly manageable, but other women can suffer major disruptions. "The impairment and reduction in quality of life for women with PMDD during their premenstrual phase is equivalent to people with major depression, anxiety disorder and even post-traumatic stress disorder," said Girdler.

While some women try antidepressants like SSRIs (selective serotonin reuptake inhibitors) to ease the symptoms, a full 40 percent don't respond well to this treatment. "We need other treatment options," Girdler said. "If we can show that continuous low-dose contraceptives are effective, that opens up another option that may have a better risk-benefit profile than SSRIs."

Women with severe premenstrual symptoms who are medically healthy and not currently taking psychotropic medicines for PMDD are invited to enroll in the trial. "Many women in our previous studies felt better knowing they were contributing to furthering our knowledge about this disorder and informing subsequent treatment options," Girdler said.

And even those who are not accepted will derive benefit from participating. "We can give them a gold-standard diagnosis if they do have PMDD; and if they have something else we can help them find treatment for it," Girdler added.

That knowledge can provide comfort to women struggling with the disorder. "Now that I've got the diagnosis," Dilweg said, "I know what to do and where to go. I have all the information and I know help is there. There's such a peace of mind from that."

There is also hope. "The more we understand, the better we can treat it, and the better for everyone," Dilweg said. "There is so much lost productivity in women with PMDD. Just think how much more a woman could accomplish if she didn't have to lose so much of herself and her energy every month."